Recent findings suggest interrelationships between obstructive sleep apnea, lipid metabolism, and neurodegeneration. Apolipoprotein E epsilon4 (APOE e4), a genetic marker linked to increased cardiovascular disease (CVD) risk and Alzheimer's disease (AD), is associated with a two fold increased risk of sleep disordered breathing (SDB), and an increase in severity of apnea symptoms. Preliminary data suggest that this association is stronger between the ages of 50 and 65. Other experiments suggest dysregulated leptin levels in obstructive sleep apnea (OSA). Taken together, these findings suggest common pathophysiological mechanisms involving dysregulated lipid metabolism in OSA. An understanding of these mechanisms is essential for the prevention and treatment of SDB. In this project, we will: 1) extend our finding that APOE e4 increases the risk of sleep apnea in the general population using case/control and family designs; 2) examine if polymorphisms in other genes regulating lipid levels are associated with sleep apnea; 3) study the relationship between lipid regulatory gene polymorphisms, lipid profile (LDL- cholesterol, HDL-cholesterol, triglycerides), plasma leptin (and other lipid regulatory hormones), and sleep apnea levels. These studies will be critical to extend our understanding of the association between sleep apnea and the metabolic syndrome. This application will focus on one arm of this complex equation, the relationship between lipid metabolism and SDB. With lipid metabolism being critical to cardiovascular risk, this application will also trigger further studies focusing on cardiovascular impact with adequate control of SDB.